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Evaluation of Two Phenanthrenemethanols for Antimalarial Activity in Man: WR 122,455 and WR 171,669^*

Two phenanthrenemethanols, WR 122,455 and WR 171,669, were tested in man for oral tolerance, toxicity, and efficacy against Plasmodium falciparum. In healthy subjects, gastrointestinal symptoms limited single-day dosage of WR 122,455 to 800 mg and WR 171,669 to 1,260 mg. No laboratory abnormalities, phototoxicity, or gastrointestinal blood loss were noted in the subjects receiving these drugs. In subjects infected with malaria, WR 122,455 cleared parasitemia when given for 1 day in doses from 440 to 880 mg; recrudescences occurred in these subjects who were infected with either chloroquine-sensitive or chloroquine-resistant P. falciparum. However, WR 122,455 at 480 mg/day for 3 to 6 days cured 9/9 cases of chloroquine-resistant and 4/4 cases of chloroquine-sensitive P. falciparum infection. WR 171,669 at 1 g/day for 3 days cured 6/6 subjects with chloroquine-resistant and 3/3 cases of chloroquine-sensitive infection. Both agents cleared parasitemia and fever promptly.

Accepted for publication April 24, 1976.

^* Address reprint requests to: Craig J. Canfield, M.D., Director, Division of Medicinal Chemistry, Walter Reed Army Institute of Research, Washington, D. C. 20012.

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